Aromatase inhibitors are the compounds that serve to reduce estradiol levels in blood by eliminating the production of estradiol through binding to and disabling the aromatase enzyme, which is responsible for the conversion (or aromatization) of androgens into estradiol. Suicidal aromatase inhibitors serve to permanently inhibit and disable the aromatase enzyme to which it is bound to. This renders the enzyme inactive forever. The body will eventually manufacture more aromatase enzymes, but the currently-bound enzymes are bound indefinitely, eliminating any risk for estrogen rebound. This is the main difference compared alongside two other major aromatase inhibitors: anastrozole and letrozole, which are non-suicidal aromatase inhibitors that are only bound to the aromatase enzyme for limited time periods. If a non-suicidal aromatase inhibitor is halted too abruptly, the circulating inhibited aromatase enzymes that have not been metabolized out of the body will then become free again, and begin aromatizing androgens into estrogens at an often rapid rate. This is not the case with Exos.
A 31-year-old man presenting with an 18-month history of sexual dysfunction resulting from severe adult-onset IHH (LH U/L, FSH U/L, T nmol/L). Initial therapy with 50 mg of clomiphene citrate (CC) three times a day for 7 days, with overnight LH pulse profiling and 9 am T levels evaluated at baseline and on completion. A 2-month washout period, followed by low-dose maintenance therapy (25-50 mg/d) for 4 months.
MAIN OUTCOME MEASURE(S):Baseline and stimulated T levels and LH pulsatility; effect on sexual function.
RESULT(S):Clomiphene therapy resulted in complete normalization of pulsatile gonadotropin secretion, serum T level, and sexual function. CONCLUSION(S):Isolated hypogonadotropic hypogonadism may result from an acquired defect of enhanced hypothalamic sensitivity to E-mediated negative feedback. Whereas direct T replacement therapy can further suppress endogenous gonadotropin secretion, treating IHH men with gonadotropins can stimulate endogenous T secretion and enhance fertility potential. On theoretical grounds, reversal of gonadotropin deficiency with CC might be expected to have a similar biological effect.
In premenopausal women, estradiol levels fluctuate throughout the menstrual cycle. Estradiol levels are at their lowest point during the early follicular phase and then rise gradually until 2-3 days before ovulation. At this point, they begin to elevate rapidly, peaking just before the ovulation-inducing surge of LH/FSH to 500%-1000% the estradiol levels seen during the early follicular phase. Afterward, levels decline modestly during the ovulatory phase before rising gradually again until the midpoint of the luteal phase. They then decline again to the trough of the early follicular phase.